At present, three-dimensional tissues are capable of being produced in vitro using various types of cells. For example, U.S. Pat. No. 5,443,950 issued to Naughton et al. describes three-dimensional cultures for bone marrow, skin, liver, vascular, and pancreatic tissues which are grown within synthetic matrices. In these tissues as well as others, investigators have been successful in proliferating cells and tissues in vitro such that the resulting three-dimensional tissues, termed "organoids" or "constructs", display many of the characteristics of their in vivo counterparts. These constructs have a variety of foreseeable applications, ranging from transplantation in vivo to functional and pharmacological testing in vitro.
In the case of skeletal muscle constructs grown in vitro, the cells generally remain in a developmentally arrested state. To maximize the usefulness of skeletal muscle constructs for basic research, clinical diagnostic applications, and pharmaceutical screening, it would be desirable to promote and control the development of the constructs, in particular the induction of full differentiation of the muscle fibers, such that the constructs more closely mimic their in vivo counterparts.
To this end, the scientific literature indicates that interventions such as the application of controlled mechanical strain and transverse electrical fields are involved in the promotion of the correct orientation and differentiation of skeletal muscle cells in culture. Applying this knowledge, there are systems that allow the application of different mechanical strain patterns to cells in culture. See, for example, U.S. Pat. Nos. 4,940,853 and 5,153,136 issued to Vandenburgh.
However, these existing cell culture systems have several deficiencies. First, the systems focus on only one type of intervention, namely the application of mechanical strain. Furthermore, the systems are not capable of readily evaluating the contractile function of skeletal muscle constructs in vitro. Without the capability to detect tissue function or properties, present systems are forced to employ preprogrammed, open-loop control of strain parameters, and therefore are not able to knowledgeably adapt the strain parameters to changes in the development of individual tissue samples.